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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02358356




Registration number
NCT02358356
Ethics application status
Date submitted
4/11/2014
Date registered
9/02/2015
Date last updated
22/11/2017

Titles & IDs
Public title
Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
Scientific title
Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study
Secondary ID [1] 0 0
CTC0120 / AG0114NET
Universal Trial Number (UTN)
Trial acronym
CONTROL NETS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Midgut Neuroendocrine Tumours 0 0
Pancreatic Neuroendocrine Tumours 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - octreotate
Treatment: Drugs - Capecitabine
Treatment: Drugs - Temozolomide

Active Comparator: PRRT - 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.

Active Comparator: CAPTEM - Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.

Experimental: PRRT/CAPTEM - 7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.


Treatment: Drugs: octreotate
7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)

Treatment: Drugs: Capecitabine
oral capecitabine 750mg/m2 b.i.d.

Treatment: Drugs: Temozolomide
temozolomide 75mg/m2 b.i.d.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival - To determine the rate of progression free survival (PFS) at 12 months in pNETs (Group A), and at 24 months in mNETs (Group B). (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).
Timepoint [1] 0 0
12 months for pNETs and 24 months for mNets
Secondary outcome [1] 0 0
Objective tumour response rate (partial or complete response) as per RECIST v1.1 criteria - To determine objective tumour response rate (OTRR) (partial or complete response (PR/CR)).
Timepoint [1] 0 0
12 months or 24 months as appropriate
Secondary outcome [2] 0 0
Overall survival (death from any cause) - To determine overall survival (OS) (death from any cause).
Timepoint [2] 0 0
12 months or 24 months as appropriate
Secondary outcome [3] 0 0
Safety (rates of adverse events worst grade according to NCI CTCAE v4.0) - To determine safety (rates of adverse events).
Timepoint [3] 0 0
12 months or 24 months as appropriate
Secondary outcome [4] 0 0
Quality of life (QOL scores determined at beginning, during treatment and until disease progression) - To determine Quality of Life (QoL) (QoL scores from EORTC QLQ C30 and QLQ-GINET21 questionnaires)
Timepoint [4] 0 0
12 months or 24 months as appropriate
Secondary outcome [5] 0 0
Resource utilisation (use of healthcare resources) and cost-effectiveness (Health utility score determined at beginning, during treatment and until end of follow up, correlated with MBS & PBS data) - To determine resource utilization (costs associated with treatment regimen, MBS and PBS data, and health utilities scores from EQ-5D-5L).
Timepoint [5] 0 0
12 months or 24 months as appropriate
Secondary outcome [6] 0 0
Clinical Benefit - To evaluate the proportion of patients who have experienced a clinical benefit of the regimen(s). (Clinical Benefit is defined as the proportion of patients who experience complete or partial response (using RECIST v1.1) or stable disease at 12 months or 24 months as appropriate).
Timepoint [6] 0 0
12 months or 24 months as appropriate

Eligibility
Key inclusion criteria
- Adults =18 years old with histologically proven, moderate to well-differentiated G1/2
pancreatic or midgut NETs with Ki-67 < 20%;

- The presence of somatostatin receptor avidity suitable for PRRT demonstrated on
68Ga-octreotate PET scan;

- Progressive advanced/metastatic disease that has progressed during or after = 2 prior
systemic therapies;

- Unresectable disease, determined by an appropriately specialized surgeon or deemed not
suitable for liver directed therapies where liver is the only site of disease;

- ECOG performance status 0-2;

- Ability to swallow oral medication;

- Adequate renal function (measured creatinine clearance > 50 ml/min by DTPA or
51CR-EDTA), bone marrow function (Hb > 9 g/d/L, ANC > 1.5 x109L, and platelets > 100 x
10/L);

- Adequate liver function (serum total bilirubin = 1.5 x ULN, and Alanine
aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) =
2.5 x ULN (= 5 x ULN for patients with liver metastases)). INR = 1.5 (or on a stable
dose of LMW heparin for >2 weeks at time of enrolment .);

- Life expectancy of at least 9 months;

- Study treatment both planned and able to start within 28 days of randomisation; )

- Willing and able to comply with all study requirements, including treatment, timing
and/or nature of required assessments;

- Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Primary NETs other than small bowel (midgut) or pancreatic NETs;

- Cytotoxic chemotherapy, targeted therapy, or biotherapy within the last four weeks;

- Prior intrahepatic 90Y microspheres, such as SIR-Spheres in the past six months;

- Prior Peptide Receptor Radionuclide Therapy;

- Major surgery/surgical therapy for any cause within one month;

- Surgical therapy of loco-regional metastases within the last three months prior to
randomisation;

- Uncontrolled metastatic disease to the central nervous system. To be eligible, CNS
metastases should have been treated with surgery and/or radiotherapy and the patient
should have been receiving a stable dose of steroids for at least 2 weeks prior to
randomisation, with no deterioration in neurological symptoms during this time;

- Poorly controlled concurrent medical illness. E.g. unstable diabetes (Note: optimal
glycaemic control should be achieved before starting trial therapy); Symptomatic NYHA
class III or IV congestive cardiac failure, myocardial infarction within 6 months of
start of the study, serious uncontrolled cardiac arrhythmia, unstable angina, or any
other clinically significant cardiac disease;

- History of other malignancies within 5 years except where treated with curative intent
AND with no current evidence of disease AND considered not to be at risk of future
recurrence Patients with a past history of adequately treated carcinoma-in-situ, basal
cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial
transitional cell carcinoma of the bladder are eligible;

- Any uncontrolled known active infection, including chronic active hepatitis B,
hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
Participants with known Hepatitis B/C infection will be allowed to participate
providing evidence of viral suppression has been documented and the patient remains on
appropriate anti-viral therapy;

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of capecitabine/temozolomide (e.g., ulcerative
disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or
substantial small bowel resection);

- Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule,
including alcohol dependence or drug abuse;

- Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal,
infertile, or use a reliable means of contraception. Women of childbearing potential
must have a negative pregnancy test done within 7 days prior to registration. Men must
have been surgically sterilised or use a (double if required) barrier method of
contraception .

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
8006 - East Melbourne
Recruitment postcode(s) [4] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Gastro-Intestinal Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Two parallel phase II randomized open label trials of Lutetium-177 Octreotate
(177Lu-Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine
(CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of
low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone
in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).
Trial website
https://clinicaltrials.gov/show/NCT02358356
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nick Pavlakis, Associate Professor
Address 0 0
Royal North Shore Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
NHMRC CTC
Address 0 0
Country 0 0
Phone 0 0
+61 (0) 2 9562 5000
Fax 0 0
Email 0 0
controlnets@ctc.usyd.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02358356